US6008376A - Aminohydroxylation of olefins with tert-alkyl sulfonamides - Google Patents
Aminohydroxylation of olefins with tert-alkyl sulfonamides Download PDFInfo
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- US6008376A US6008376A US09/138,303 US13830398A US6008376A US 6008376 A US6008376 A US 6008376A US 13830398 A US13830398 A US 13830398A US 6008376 A US6008376 A US 6008376A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D203/00—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom
- C07D203/04—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D203/06—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D203/22—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to the ring nitrogen atom
- C07D203/24—Sulfur atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D203/00—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom
- C07D203/26—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
Definitions
- the present invention relates to tert-alkyl sulfonamide chloramine salts and the use of such salts as nitrogen sources in the catalytic aminohydroxylation and/or aziridination of olefins.
- the resulting tert-alkyl sulfonamide group can be removed from the aminohydroxylation and/or aziridination product under mild conditions to form an unsubstituted hydroxy-amine and aziridine product.
- Chlorosulfonamide salts such as Chloramines T and M
- Chloramines T and M have been extensively used as nitrogen sources in both asymmetric and racemic aminohydroxylations, aziridinations and allylic aminations (Bruncko et al. Angew. Chem., Int. Ed. Engl. 1996, 35, 454; Li et al. Angew. Chem., Int. Ed. Engl. 1996, 35, 451; Rubin et al. Angew. Chem., Int. Ed. Engl. 1997, 36, 2637).
- the removal of the alkyl- or arylsulfonyl group from the introduced sulfonylamino group is often very problematic and requires extremely harsh conditions.
- Weinreb and co-workers published a communication of a new protective group for amine: t-butylsulfonyl substituted amines were found to be stable under a variety of conditions, however the t-BuSO 2 -group could be easily removed under relatively mild acidic conditions (sun et al. J. Org. Chem. 1997, 62, 8604).
- Weinreb did not prepare the chloramine salt of t-butylsulfonamide or demonstrate that it could be employed t as a nitrogen source in aminohydroxylation and aziridination of olefins.
- One aspect of the invention is directed to a process for converting an olefinic substrate to a tert-alkyl-sulfonamide substituted aziridine.
- a tert-alkyl-sulfonamide chloramine salt is employed as a nitrogen source in a catalytic addition reaction for converting the olefinic substrate into the tert-alkyl-sulfonamide substituted aziridine.
- phenyltrimethylammonium tribromide is employed as the catalyst.
- Another aspect of the invention is directed to a process for converting an olefinic substrate to an asymmetric ⁇ -substituted amine product.
- a tert-alkyl-sulfonamide chloramine salt is employed as a nitrogen source in a catalytic addition reaction for catalytically converting the olefinic substrate into a tert-alkyl-sulfonamide substituted aziridine.
- the tert-alkyl-sulfonamide substituted aziridine is then opened with a nucleophile for forming an ⁇ -substituted tert-alkyl-sulfonamide intermediate.
- the ⁇ -substituted tert-alkyl-sulfonamide intermediate is deprotected for forming the asymmetric ⁇ -substituted amine product.
- the catalyst is phenyltrimethylammonium tribromide.
- the ⁇ -substituted tert-alkyl-sulfonamide intermediate is deprotected using a mild acid.
- Another aspect of the invention is directed to an improved process for converting an olefinic substrate to an asymmetric hydroxylamine product.
- the process is of a type which includes a catalytic asymmmetric aminohydroxylation step and a deprotection step.
- the catalytic asymmmetric aminohydroxylation step employs a nitrogen source and a hydroxyl source for transforming said olefinic substrate into an an asymmetric hydroxy-tert-alkyl-sulfonamide intermediate.
- the improvement is directed to the use of a tert-alkyl-sulfonamide chloramine salt as the nitrogen source during the catalytic asymmmetric aminohydroxylation step and to the hydrolyzation of the asymmetric hydroxy-tert-alkyl-sulfonamide intermediate during the deprotection step for producing the asymmetric hydroxylamine product.
- a reaction solution is employed during catalytic asymmmetric aminohydroxylation step which includes the olefinic substrate, the nitrogen source, a hydroxyl radical source, osmium as a catalyst, and a chiral ligand for enantiomerically directing said asymmetric addition.
- the asymmetric hydroxy-tert-alkyl-sulfonamide intermediate is hydrolyzed with mild acid during the deprotection step.
- a preferred mild acids include a 0.01-0.5 molar solution of triflic acid (TfOH) and a 0.01-0.5 molar solution of trifluoroacetic acid (TFA), each having an approximate PKa value in the range of 2-4.
- tert-alkyl-sulfonamide chloramine salt employable in an aminohydroxylation reaction.
- the tert-alkyl-sulfonamide chloramine salt is represented by the following structure: ##STR1## wherein R 1 is a tertiary-alkyl group.
- Preferred tertiary-alkyl groups include --C(CH 3 ) 3 , --C(CH 3 ) 2 --(CH 2 ) n --(C(CH 3 ) 3 ), C(CH 3 ) 2 --(CH 2 ) n --CH 3 , --C(CH 3 ) 2 --(CH 2 ) n --C(CH 3 ) 2 --(CH 2 ) n --C(CH 3 ) 2 --(CH 2 ) n --CH 3 , and --C(CH 3 ) 2 --(CH 2 ) n --CH 3 , wherein 0 ⁇ n ⁇ 8.
- Another aspect of the invention is directed to a process for synthesizing a tert-alkyl sulfonamide chloramine salt represented by the following structure: ##STR2##
- a bis-tert-alkyl-disulfide is oxidized with an oxidizing agent for forming a tert-alkyl disulfide oxide intermediate.
- the bis-tert-alkyl-disulfide is represented by the following structure: ##STR3## wherein R 1 is a is a tertiary-alkyl group.
- the tert-alkyl disulfide oxide intermediate being represented by the following structure: ##STR4## Then, the above tert-alkyl disulfide oxide intermediate is chlorinated with sulfuryl chloride for forming a tert-alkyl sulfonyl chloride represented by the following structure: ##STR5## Then, the above tert-alkyl sulfonyl chloride is reacted with sodium azide for forming a tert-alkyl sulfonamide represented by the following structure: ##STR6## Finally, the above tert-alkyl sulfonamide is treated with a hypochlorite and sodium hydroxide for producing the tert-alkyl-sulfonamide chloramine salt.
- FIG. 1 illustrates the following: (1A)represents the conventional method of synthesis of sulfonamides which includes a reaction of ammonia with sulfonyl chlorides prepared from the corresponding sulfonic acids; (1B) shows that if sodium azide (instead of hydroxylamine) provides a much more efficient way to accomplish the direct conversion of 1 to 2; the reaction is conducted in refluent acetonitrile containing small amount of water; (1C) shows that the intermediate t-butyl sulfinyl chloride can be prepared from commercially available bis-t-butyl disulfide in two steps with the indicated reaction conditions shown in the scheme.
- FIG. 2 illustrates the aminohydroxylation of ⁇ , ⁇ -unsaturated amides with the following reaction conditions: admixed olefin, BusNClNa (2) (1.2 eq.), K 2 OsO 2 (OH) 4 (0.5 mol%), t-BuOH-H 2 O 1:1, r.t and stirred for 12 hrs followed by standard work-up and purification; (*) represents ratios in isolated product.
- TFOH triflic acid
- TFA solution 0.01-0.5 Molar TFA solution
- FIG. 5 illustrates various di-tert-octyl disulfides as the precursers for tert-alkyl sulfonamide chloramine salts obtained via the two step procedure as shown in FIG. 1, steps B and C.
- the invention is directed to the use and synthesis of an effective nitrogen source of the type R--N.sup.(-) --Hal with an easily cleavable R--N bond wherein R is a tertiary alkyl group. Furthermore, the invention is directed to the use of such nitrogen sources in both catalytic aminohydroxylation and aziridination of olefins.
- t-Butyl sulfonamide in particular, has been shown to be an efficient nitrogen source in aminohydroxylation and aziridination of olefins close to Chloramine T by its properties and behavior.
- the resulting t-butyl sulfonylamino functionality can be easily converted to an unprotected amine under mild acidic conditions.
- the synthesis of t-butyl sulfonamide has been accomplished on a multigram scale from cheap and readily available starting materials and reagents.
- the conventional method of synthesis of sulfonamides includes a reaction of ammonia with sulfonyl chlorides, which are usually easily prepared from the corresponding sulfonic acids (FIG. 1A).
- This path can be efficiently used to make primary and secondary alkyl sulfonamides as well as aryl and heteroaryl sulfonamides.
- the instability of tertiary alkyl sulfonyl chlorides as well as their principally different mode of reactivity toward nucleophiles make this path inapplicable for the synthesis of tert-alkyl sulfonamides (King et al. J. Org. Chem. 1995, 60, 2831).
- the sulfur-nitrogen bond in this case has to be created with a lower oxidation state sulfur derivative.
- tert-butylsulfonamide 1 is a fairly stable compound and can be oxidized to 2 with a variety of reagents.
- a number of approaches to the synthesis of 1 is documented in the literature, including reactions of t-butylsulfinyl chloride 3 with ammonia or bis-(t-butyl)disulfide oxide 4 with lithium amide. More appealing, however, was the method developed by Hovius and Engberts, who found that addition of hydroxylamine to 1 leads directly to sulfonamide 2 (Hovius et al. Tetrahedron Lett. 1972, 181). Unfortunately, the method requires use of the free base of hydroxylamine, which is very unstable.
- disulfide can be used to make the desired intermediate t-alkyl sulfinyl chloride in two steps as shown in FIG. 1C (scheme) and FIG. 5 (disulfides).
- Available disulfides include but are not restricted to di-tert-octyl disulfide, di-tert-tetradecyl-disulfide, di-tert-amyl-disulfide and di-tert-dodecyl-disulfide (the tert-alkyl sulfonamide is then synthesized exactly as for t-butyl case in two steps as shown in FIGS. 1B and 1C (Netscher et al. Synthesis 1987, 683)).
- tert-alkyl sulfonamide chloramine salt is then accomplished via standard methods known in the art and includes the treatment of the tert-alkyl-sulfonamide (eg. Bus-NH 2 (2)) with 1 equivalent of t-butyl hypochlorite and 1 equivalent of sodium hydroxide to give the corresponding chloramine salt (conditions are outlined in Rudolph et al. Angew. Chem., Int. Ed. Engl. 1996, 35, 281).
- Aziridination is carried out in acetonitrile at room temperature with 10 mol% of PTAB.
- the products and the yields of aziridination of a series of alkenes is presented in FIG. 3.
- aminohydroxylation the results closely resemble those we obtained with Chloramine T.
- the yields are generally high for unfunctionalized olefins.
- the studies are currently under way to evaluate the effect of various functionalities on the outcome of the reaction.
- Analytical thin layer chromatography was performed using pre-coated glass-backed plates (Merck Kieselgel F 254 ) and visualized by cerium molybdophosphate or ninhydrin. Diethyl ether, tetrahydrofuran (THF) and toluene (PhCH 3 ) were distilled from sodium-benzophenone ketyl, dichloromethane (DCM) and acetonitrile from calcium hydride. Other solvents and reagents were purified by standard procedures if necessary.
- tert-alkyl sulfonamide chloramine salt is accomplished via standard methods known in the art and includes the treatment of the tert-alkyl-sulfonamide (eg. Bus-NH 2 (2)) with 1 equivalent of t-butyl hypochlorite and 1 equivalent of sodium hydroxide to give the corresponding chloramine salt 6 (conditions are outlined in Rudolph et al. Angew. Chem., Int. Ed.
- tert-alkyl sulfonamide chloramine salt is accomplished via standard methods known in the art and includes the treatment of the tert-alkyl-sulfonamide (with 1 equivalent of t-butyl hypochlorite and 1 equivalent of sodium hydroxide to give the corresponding chloramine salt (conditions are outlined in Rudolph et al. Angew. Chem., Int. Ed. Engl. 1996, 35, 281).
- sulfonamides are commercially available. Others are prepared from commercially available sulfonyl chlorides: Reaction conditions: (a) NH3 (g), CH 2 Cl 2 , RT; (b) aqueous NH3, acetone, RT. Typical experimental procedure using gaseous ammonia: The sulfonyl chloride (1000, 10 mmol) is added slowly, in portions, to a stirred saturated solution of NH 3 in CH 2 Cl 2 (10 mL) at room temperature (NH 3 (g) bubbled through the solvent beforehand). After the complete addition of 10, NH 3 (g) is bubbled through the the reaction for a further 30 min.
- reaction mixture was worked up using standard workup conditions. A typical procedure may be carried out as follows: The reaction mixture was concentrated (about up to 1/10 volume) and filtered through a short column of silica gel (4 ⁇ 4 cm, 10% EtOAc in hexane). After evaporation of the solvent, the resultant solid was purified by recrystallization in hexane to give 710 mg (93%) of aziridine as colorless crystals. Modified workup: The reaction mixture was diluted with ethyl acetate (40 ml) and water (40 ml). The organic layer was separated and washed with brine (20 ml), followed by drying over MgSO4.
- t-alkylsulfonylamides obtained from by AA and aziridiation are deprotected under conditions developed by Weinreb (Sun, P.; Weinreb, S. M. J. Org. Chem. 1997, 62, 8604).
- the Bus-protected primary amide gave high yields of the unprotected amine upon treatment with 0.1 Molar triflic acid/methylene choride with 20 equivalents anisole at 0° C. to room temperature over 2-5 hr range.
- Attempts to deprotect the aziridine by treating it with trifluoroacetic acid were unsuccessful as aziridine opening occurred easily under those conditions as shown in FIG. 4.
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Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20030161860A1 (en) * | 2002-02-07 | 2003-08-28 | Taneja Subhash Chandra | Novel substituted aryl alkenoic acid heterocyclic amides |
US20040254066A1 (en) * | 2001-07-12 | 2004-12-16 | Chandrashekar Ramarao | Microencapsulated catalyst methods of preparation and method of use thereof |
US20050010068A1 (en) * | 2001-12-01 | 2005-01-13 | Holmes Andrew Bruce | Use of microencapsulated transition metal reagents for reactions in supercritical fluids |
US8987504B2 (en) | 2010-06-18 | 2015-03-24 | Victoria Link Limited | Aminohydroxylation of alkenes |
WO2015103505A3 (en) * | 2014-01-03 | 2015-07-30 | Ess Daniel Halsell | Direct stereospecific synthesis of unprotected aziridines from olefins |
-
1998
- 1998-08-21 US US09/138,303 patent/US6008376A/en not_active Expired - Lifetime
Non-Patent Citations (11)
Title |
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Bruncko, et al., "Allylic Amination and 1,2-Diamination with a Modified Diimidoselenium Reagent", Angew. Chem. Int. Ed. Engl., 35(4):454-456 (1996). |
Bruncko, et al., Allylic Amination and 1,2 Diamination with a Modified Diimidoselenium Reagent , Angew. Chem. Int. Ed. Engl ., 35(4):454 456 (1996). * |
CA70: 86837 Substituted aziridines. Relative rates . . . opening. Stephens et al. 1969. * |
King, et al., "tert-Butyl Cation Formation in the Hydrolysis of 2-Methyl-2-propanesulfonyl Chloride, the Simplest Tertiary Alkanesulfonyl Chloride", J. Org. Chem., 60:2831-2834 (1995). |
King, et al., tert Butyl Cation Formation in the Hydrolysis of 2 Methyl 2 propanesulfonyl Chloride, the Simplest Tertiary Alkanesulfonyl Chloride , J. Org. Chem ., 60:2831 2834 (1995). * |
Li, et al., "Catalytic Asymmetric Aminohydroxylation (AA) of Olefins", Angew. Chem. Int. Ed. Engl., 35(4):451-454 (1996). |
Li, et al., Catalytic Asymmetric Aminohydroxylation (AA) of Olefins , Angew. Chem. Int. Ed. Engl ., 35(4):451 454 (1996). * |
Rubin, et al., "A Highly Efficient Aminohydroxylation Process", Angew. Chem. Int. Ed. Engl., 36(23):2637-2640 (1997). |
Rubin, et al., A Highly Efficient Aminohydroxylation Process , Angew. Chem. Int. Ed. Engl ., 36(23):2637 2640 (1997). * |
Sun, et al., "tert-Butylsulfonyl (Bus), a New Protecting Group for Amines", J. Org. Chem., 62:8604-8608 (1997). |
Sun, et al., tert Butylsulfonyl (Bus), a New Protecting Group for Amines , J. Org. Chem ., 62:8604 8608 (1997). * |
Cited By (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040254066A1 (en) * | 2001-07-12 | 2004-12-16 | Chandrashekar Ramarao | Microencapsulated catalyst methods of preparation and method of use thereof |
US8828902B2 (en) | 2001-07-12 | 2014-09-09 | Reaxa Limited | Microencapsulated catalyst methods of preparation and method of use thereof |
US20050010068A1 (en) * | 2001-12-01 | 2005-01-13 | Holmes Andrew Bruce | Use of microencapsulated transition metal reagents for reactions in supercritical fluids |
US20030161860A1 (en) * | 2002-02-07 | 2003-08-28 | Taneja Subhash Chandra | Novel substituted aryl alkenoic acid heterocyclic amides |
WO2003070713A1 (en) * | 2002-02-07 | 2003-08-28 | Council Of Scientific And Industrial Research | Substituted aryl alkenoic acid heterocyclic amides possessing pungent taste |
US20060094874A1 (en) * | 2002-02-07 | 2006-05-04 | Council Of Scientific And Industrial Research | Novel substituted aryl alkenoic acid heterocyclic amides |
US7057040B2 (en) * | 2002-02-07 | 2006-06-06 | Council Of Scientific And Industrial Research | Substituted aryl alkenoic acid heterocyclic amides |
US7262296B2 (en) | 2002-02-07 | 2007-08-28 | Council Of Scientific And Industrial Research | Substituted aryl alkenoic acid heterocyclic amides |
AU2002234820B2 (en) * | 2002-02-07 | 2008-09-11 | Council Of Scientific And Industrial Research | Substituted aryl alkenoic acid heterocyclic amides possessing pungent taste |
US8987504B2 (en) | 2010-06-18 | 2015-03-24 | Victoria Link Limited | Aminohydroxylation of alkenes |
WO2015103505A3 (en) * | 2014-01-03 | 2015-07-30 | Ess Daniel Halsell | Direct stereospecific synthesis of unprotected aziridines from olefins |
US9988349B2 (en) | 2014-01-03 | 2018-06-05 | Daniel Halsell ESS | Direct stereospecific synthesis of unprotected aziridines from olefins |
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